ERASER: Safety and Preliminary Efficacy of ATG-017 Monotherapy in Advanced Solid Tumors and Hematological Malignancies
Study Details
Study Description
Brief Summary
This is a Phase I, multi-center, open-label study of ATG-017 administered orally, alone in patients with advanced solid tumors and hematological malignancies. The study design includes a Dose Escalation Phase and Dose Expansion Phase.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The dose escalation of ATG 017 with intensive safety monitoring to ensure the safety of the patients with solid tumors (solid tumors group) and hematological malignancies (hematological malignancies group) harbouring activating alterations in the RAS-MAPK pathway. Dose Expansion Phase will begin at the defined maximum tolerated dose (MTD) and/or biologically effective dose and/or other dose, in order to further evaluate the safety, tolerability and PDx of ATG 017. Patients with solid tumors or hematological malignancies harbouring activating alterations in the RAS-MAPK pathway will be enrolled.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ATG-017 ATG-017 will be administered orally on an empty stomach QD in the first cohort of solid tumors group and BID 12 hours apart (no food or drink other than water for 2 hours prior to, and for 1 hour after study treatment administration) in other cohorts. All doses of ATG-017 should be taken at approximately the same time each day. Patients will receive study treatment in 21-day cycles. |
Drug: ATG-017
Dosing will begin at 5 mg once a day (QD) ATG-017 as starting dose. A cycle of study treatment will be defined as 21 days.
Other Names:
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Outcome Measures
Primary Outcome Measures
- AEs/SAEs [18 months]
Toxicity will be graded according to the NCI CTCAE, Version 5.0.
Secondary Outcome Measures
- Plasma concentrations [18 months]
Venous blood samples for determination of total concentrations of ATG 017 in plasma to characterise the PK profile of ATG-017 for a particular dose level
- Overall Response Rate (ORR) [18 months]
To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006
- DOR [18 months]
Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented
- Progression-Free Survival (PFS) [18 months]
The time from the first dose date until disease progression or death from any cause
Other Outcome Measures
- Level of phospho-p90RSK [18 months]
Blood samples will be analysed for the level of phospho-p90RSK
- Level of transcript biomarker [18 months]
Blood samples will be analysed for the level of DUSP6
- Level of phospho-ERK [18 months]
Blood samples will be analysed for the level of phospho-ERK
- Level of total ERK [18 months]
Blood samples will be analysed for the level of total ERK
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
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Aged at least 18 years.
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Patient must have a documented activating alteration of the RAS-MAPK pathway.
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Histological or cytological confirmation of a solid tumour.
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Patients with hematological malignancies.
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Patient with solid tumors must have at least 1 lesion, not previously irradiated.
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Estimated life expectancy of minimum of 12 weeks.
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Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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Ability to swallow and retain oral medication.
Exclusion Criteria:
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Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.
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Prior ATG-017 administration in the present study.
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Prior treatment with an ERK1/2 inhibitor.
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Prior major surgery within 28 days of the first dose of study treatment or minor surgical procedures ≤7 days.
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Patients receiving unstable or increasing doses of corticosteroids.
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As judged by the investigator, any evidence of severe or uncontrolled systemic diseases.
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Active infection including hepatitis B, and/or hepatitis C.
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Known history of human immunodeficiency virus (HIV) infection.
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Inadequate bone marrow reserve or organ function
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peter MacCallum Cancer Centre | East Melbourne | Victoria | Australia | 3002 |
| 2 | Austin Hospital | Heidelberg | Victoria | Australia | 3084 |
| 3 | Alfred Hospital | Melbourne | Victoria | Australia | 3004 |
| 4 | Scientia Clinical Research | Randwick | Australia | ||
| 5 | Chris O'Brien Lifehouse | Sydney | Australia |
Sponsors and Collaborators
- Antengene Therapeutics Limited
Investigators
- Study Director: Sai Lou, MD, Medical Monitor
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ATG-017-001